Dr. Shade's Bitter X [Discontinued] by Quicksilver Scientific

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. Although there has been interest in using oral dandelion for constipation, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Dyspepsia. Although there has been interest in using oral dandelion for dyspepsia, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Flatulence. Although there has been interest in using oral dandelion for flatulence, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Heart failure. Although there has been interest in using oral dandelion for its diuretic effects in patients with heart failure, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Joint pain. Although there has been interest in using oral or topical dandelion for joint pain, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Tonsillitis. It is unclear if oral dandelion is beneficial in patients with tonsillitis. Details: One small clinical study in patients with acute purulent tonsillitis shows that eating soup containing dandelion (pugongying soup) daily for 3 days along with benzylpenicillin sodium 640,000 units daily improves recovery when compared with placebo plus benzylpenicillin sodium. Recovery rates were 36% with the dandelion-containing soup compared to 10% with placebo (18292).
• Urinary tract infections (UTIs). Oral dandelion has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with recurrent UTIs shows that taking a specific combination of dandelion root and uva ursi leaf extracts three times daily for 1 month reduces the risk of UTI recurrence when compared with placebo at 12-month's follow-up. For every 5 patients treated with this combination over placebo, one additional UTI was prevented (1932). In this combination, uva ursi is used for its antibacterial properties and dandelion is used to increase urination. However, this combination is not recommended for extended use because uva ursi may be unsafe when used long-term. Another small clinical study in premenopausal females with acute, uncomplicated lower UTIs shows that taking a combination product containing dandelion extract 50 mg, D-mannose, prebiotics, arabinogalactan, and astragalus root extract twice daily for five days, along with phenazopyridine and alkylating agents as conventional therapy, improves UTI symptoms and bacteriuria when compared with placebo plus conventional therapy (111757). It is unclear if these effects are due to dandelion, other ingredients, or the combination. More evidence is needed to rate dandelion for these uses.

(Read more about DANDELION)

POSSIBLY EFFECTIVE

• Sinusitis. Clinical research shows that taking gentian orally in a specific combination product (SinuComp; Sinupret) that also contains elderflower, verbena, cowslip flower, and sorrel improves the symptoms of acute or chronic sinusitis (374,379). In one cohort study, taking this specific combination product orally three times daily with mometasone furoate nasal spray 200 mcg twice daily for 7 days reduces symptoms related to acute sinusitis when compared with using mometasone nasal spray alone (95907).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Weight loss. Preliminary clinical research in healthy adults shows that consuming a pudding containing microencapsulated gentian root extract 1.25 g at breakfast modestly reduces caloric intake over 24 hours, but does not affect self-reported feelings of hunger or fullness, when compared with placebo pudding (96534). More evidence is needed to rate gentian for this use.

(Read more about GENTIAN)

LIKELY INEFFECTIVE

• Schistosomiasis. Most research suggests that oral myrrh extract is not effective for treating schistosomiasis. Details: Although one manufacturer-sponsored study shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 600 mg once daily for 6 days cures schistosomiasis in about 90% of patients, multiple clinical studies show that taking this myrrh extract does not treat schistosomiasis in children or adults. In one study, only about 9% of adults and children treated with this myrrh extract at a dose of 600 mg every 3 weeks for 2 doses were cured compared to about 76% of patients treated with praziquantel (95541). A similar lack of benefit was shown in another clinical trial in which children were given a higher dose of 300 mg daily for 3 days or 600 mg daily for 6 days (95542,95545). A systematic review of the available literature concludes that praziquantel continues to be the treatment of choice for schistosomiasis, and that myrrh appears ineffective for parasitological cure (95544).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Back pain. It is unclear if oral myrrh is beneficial in patients with back pain, and topical myrrh has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with chronic low back pain shows that two 15-minute sessions of lumbar massage weekly with 5 mL of myrrh 2% and frankincense 2% essential oils for 3 weeks reduces measures of pain and disability when compared with placebo (111504). An observational study in adults with chronic lower back pain and sciatica suggests that taking a combination of myrrh 200 mg, palmitoylethanolamide 600 mg, and alpha-lipoic acid 800 mg daily for 30 days, along with periradicular infiltrations of oxygen-ozone, is associated with resolution of pain in 17% more patients when compared with periradicular steroid infiltrations at 60 days (111308). However, it is unclear if the effects in these studies are due to myrrh, other ingredients, or the combinations. Additionally, observational research in adults with chronic low back pain of varying intensity has found that taking a specific myrrh extract (MyrliMax, Sundyota Numandis Pharmaceuticals) 100 mg twice daily for 20 days is associated with reductions in pain and the need for rescue analgesics when compared to baseline (111112). The validity of these findings is limited by the lack of a control group.
• Cancer. Although there has been interest in using oral myrrh for cancer, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Canker sores. Although there has been interest in using topical myrrh for canker sores, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Common cold. Although there has been interest in using oral myrrh for the common cold, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Cough. Although there has been interest in using oral myrrh for cough, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Crohn disease. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research over a period of 24-28 days in a small group of patients with active inflammatory bowel disease (50% ulcerative colitis and 50% Crohn disease) has found that taking a specific combination product containing myrrh 100 mg, coffee charcoal 50 mg, and chamomile extract 70 mg per tablet (MYRRHINIL-INTEST, Repha GmbH) results in symptom resolution in 16-26 days. The probability of being free of symptoms did not differ between patients using other treatments, the myrrh combination product alone, or a combination of the myrrh product with other treatments. Overall efficacy was rated as good to very good by patients and physicians (104593). The validity of these findings is limited by the observational nature of the study. Also, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Dental peri-implantitis. It is unclear if rinsing with myrrh mouthwash solution is effective for the prevention of dental peri-implantitis. Details: A small clinical study in adults undergoing dental implant placement shows that rinsing with myrrh 1% mouthwash solution twice daily for 2 weeks leads to similar rates of postoperative bleeding, pain, redness, and swelling when compared with chlorhexidine 0.12% mouthwash (111114).
• Diarrhea. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research over a period of 7-14 days in a group of patients with active diarrhea related to an acute inflammatory disorder has found that taking a specific combination product containing myrrh 100 mg, coffee charcoal 50 mg, and chamomile extract 70 mg per tablet (MYRRHINIL-INTEST, Repha GmbH), alone or in combination with other therapies, improves overall symptoms of diarrhea. The median time to symptom resolution was 4 days. The probability of symptom resolution with use of the myrrh combination product was similar to that observed when other treatments were used. Overall efficacy was rated as good to very good by patients and physicians (104593). The validity of these findings is limited by the observational nature of the study. Also, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Fasciolosis. It is unclear if oral myrrh extract is beneficial in patients with fasciolosis. Details: A small clinical study in adults and children with fasciolosis shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 600 mg daily for 6 days leads to a cure rate of about 94% at 3 months. However, the lack of standardized stool sample evaluation and absence of a control group limit the validity of this finding (95543). Furthermore, another small study in adults and children with fasciolosis shows that taking this same product, 600 mg daily for 6 days, leads to a 0% cure rate at both 1 and 2 months (95545).
• Gingivitis. Although there has been interest in using topical myrrh for gingivitis, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Herniated disc. Oral myrrh has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small observational study in adults with acute lumbosacral radiculopathy secondary to lumbar disc herniation suggests that taking a combination supplement containing myrrh 100 mg, alpha-lipoic acid 404 mg, and palmitoylethanolamide (PEA) 306 mg (Tiobec Dol, Uriach Italy Srl) twice daily for 4 weeks, along with steroids and as needed opioids, is associated with reduced pain and disability and improved physical but not mental health as it pertains to quality of life when compared with steroids and as needed opioids alone (111711). However, it is unclear if these effects are due to alpha-lipoic acid, other ingredients, or the combination.
• Intestinal parasite infection. It is unclear if oral myrrh extract is beneficial in children with intestinal parasite infections. Details: A small clinical study in immunocompetent children shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 10 mg/kg daily in combination with paromomycin 500 mg four times daily for 2 weeks improves symptoms such as abdominal pain, diarrhea, nausea, and vomiting when compared with paromomycin or myrrh extract alone. However, no differences in oocyst elimination were observed across groups (95546).
• Irritable bowel syndrome (IBS). Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research over a period of 24-28 days in a group of patients with IBS has found that taking a specific combination product containing myrrh 100 mg, coffee charcoal 50 mg, and chamomile extract 70 mg per tablet (MYRRHINIL-INTEST, Repha GmbH), alone or in combination with other therapies, improves overall symptoms of diarrhea. The probability of being free of symptoms did not differ between patients using other treatments or when the myrrh combination product was used in combination with other treatments. Overall efficacy was rated as good to very good by patients and physicians (104593). The validity of these findings is limited by the observational nature of the study. Also, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Miscarriage. It is unclear if oral myrrh is beneficial in patients with incomplete miscarriage. Details: A small clinical study in adults with incomplete miscarriage (incomplete abortion) shows that taking myrrh 500 mg three times a day for 2 weeks increases the proportion of patients with successful complete abortion, defined as no retained products of conception, to 83%, compared to only 54% of those taking placebo (104840).
• Muscle cramps. Although there has been interest in using oral myrrh for muscle cramps, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Oral mucositis. Although there has been interest in using topical myrrh for oral mucositis, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Pain (acute). It is unclear if oral myrrh extract is beneficial in patients with acute pain. Details: A small clinical study shows that taking a specific, standardized myrrh extract (MyrLiq, Biosfered S.r.l.) 200-400 mg daily for 20 days can improve various types of acute pain, including headache, fever-associated pain, joint or muscle pain, lower back pain, and menstrual cramps, when compared with placebo (98224).
• Pain (chronic). It is unclear if oral myrrh extract is beneficial in patients with chronic pain. Details: A small clinical study shows that taking a specific, standardized myrrh extract (MyrLiq, Biosfered S.r.l.) 200-400 mg daily for 20 days can improve various types of chronic pain, including joint or muscle pain and lower back pain, when compared with placebo (98224).
• Peptic ulcers. Although there has been interest in using oral myrrh for peptic ulcers, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Sciatica. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research in patients with sciatic pain due to herniated discs has found that taking a combination of myrrh extract 200 mg, alpha-lipoic acid 800 mg, and palmitoylethanolamide 600 mg daily for 20 days along with 3 sessions of oxygen-ozone therapy over 30 days is associated with slight improvements in pain when compared with oxygen-ozone therapy alone (111113). The validity of these findings is limited by the observational nature of the study. Additionally, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Tooth extraction. It is unclear if rinsing with myrrh extract solution is beneficial in patients undergoing tooth extraction. Details: A small clinical study in healthy, non-smoking adults shows that using a mouthwash containing myrrh extract 0.5% twice daily for 7 days following simple tooth extraction decreases the socket size in 90% of patients compared with 40% in the control group. Swelling and tenderness also decreased when compared with control (105846).
• Trichomoniasis. It is unclear if oral myrrh extract is beneficial in patients with trichomoniasis. Details: A small clinical study in patients with resistant Trichomonas vaginalis shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 600 mg daily for 6-8 days cures infections in most patients. In this small study, 85% (11/13) of patients who did not respond to combination therapy with metronidazole and tinidazole were cured after receiving this myrrh extract (93652). A lack of control group limits the validity of these findings.
• Ulcerative colitis. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: A small clinical study in patients with ulcerative colitis shows that taking a specific combination product containing myrrh 100 mg, chamomile extract 70 mg, and coffee charcoal 50 mg per tablet (MYRRHINIL-INTEST, Repha GmbH), four tablets three times daily for 12 months, is non-inferior to mesalamine therapy for maintaining remission (93653). In addition, observational research over a period of 24-28 days in a small group of patients with active inflammatory bowel disease (50% ulcerative colitis and 50% Crohn disease) has found that taking this same product results in symptom resolution in 16-26 days. The probability of being free of symptoms did not differ between patients using other treatments, the myrrh combination product alone, or the myrrh combination product with other treatments. Overall efficacy was rated as good to very good by physicians (104593). It is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Urinary tract infections (UTIs). Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: A small clinical study in patients with at least 2 recurrent UTIs in the past 6 months or more than 3 UTIs in the past year shows that taking a combination of myrrh, hibiscus, and vegetable proteases (Aviur Retard ) for 6 months might reduce the risk of UTI recurrence. A UTI episode was not reported by 49% of females over the 6-month period, with an additional 35% reporting fewer than 2 UTIs (101115). The validity of these findings is limited by the lack of comparator group. Additionally, it unclear if this benefit is due to myrrh, other ingredients, or the combination.
• Wound healing. It is unclear if topical myrrh extract is beneficial for wound healing. Details: Two small clinical studies in patients requiring episiotomy during childbirth shows that using myrrh 1:5 tincture 10 mL or myrrh extract 20 mL, diluted in 5 L of water as a sitz bath, twice daily for 7 days, modestly improves ecchymosis, discharge, and wound healing scores when compared with either placebo, frankincense extract 20 mL, or betadine 10% solution 20 mL (104838,104839). It is unclear if these modest effects are clinically relevant. More evidence is needed to rate myrrh for these uses.

(Read more about MYRRH)

POSSIBLY EFFECTIVE

• Ulcerative colitis. Clinical research suggests that taking slow-release, phosphatidylcholine-rich phospholipids (Sterpur P-30 Granulat, Stern-Lecithin and Soja GmbH) improves symptoms and remission rate in patients with ulcerative colitis (68839,93389,93390,105728). A pooled analysis of 3 small randomized clinical trials in adults with chronic, active, ulcerative colitis at a single site shows that taking this specific form of phosphatidylcholine 1-4 grams daily for 3 months increases the odds of achieving clinical remission by 9.7 times when compared with placebo. Overall, 49% of the patients taking phosphatidylcholine achieved clinical remission. Taking phosphatidylcholine also improved quality of life and clinical improvement scores. In one study, this product also decreased the need for steroids, resulting in complete withdrawal of steroid therapy without exacerbation of disease in 80% of patients (93390). However, most patients in these studies were not treated with other standard therapies for ulcerative colitis, such as immunosuppressants and aminosalicylic acids. Subgroup analyses by dose suggest that the effective dose of this product is at least 1 gram daily; however, taking 3-4 grams daily may be more effective (93389,105728). In patients not responsive to mesalamine, some preliminary clinical research suggests taking LT-02 (Lipid Therapeutics GmbH), a modified-release formula of phosphatidylcholine, 3.2 grams daily for 12 weeks, improves symptoms of ulcerative colitis. Overall disease activity was improved by 52%, compared with 33% in those taking placebo. The effects on remission rate and mucosal healing were unclear; however, response rates were increased from 60% in the placebo group to 83% in the phosphatidylcholine group. In an 8-week follow-up, relapse was also less likely in patients treated with this product (93387).

POSSIBLY INEFFECTIVE

• Hepatitis A. Taking phosphatidylcholine orally does not seem to reduce serum bilirubin or liver enzyme levels in patients with hepatitis A (5225).
• Infant development. Clinical research suggests that taking phosphatidylcholine (PhosChol, Nutrasal) 5 grams daily, containing choline 750 mg daily, from 18 weeks' gestation to 90 days postpartum does not improve cognitive function in the infant at 10-12 months of age when compared with corn oil placebo (93386).
• Peritoneal dialysis. Taking phosphatidylcholine orally does not seem to improve ultrafiltration in peritoneal dialysis (5222).
• Tardive dyskinesia. Taking phosphatidylcholine orally does not seem to improve tardive dyskinesia (5223).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Preliminary clinical research suggests that topical application of a cream containing niacinamide and linoleic acid-rich phosphatidylcholine (4% niacinamide-phospholipidic; N-PHCL emulsion) once daily for 12 weeks appears to improve skin hydration and reduce acne lesions and inflammation when compared with a 1% clindamycin cream or a carrier-only cream in patients 15 years and older with moderate acne (93388).
• Alcohol-related liver disease. Preliminary clinical research suggests that taking polyunsaturated phosphatidylcholine 6 grams daily for 24 months does not increase survival compared to placebo in patients with acute alcoholic hepatitis (68843).
• Dementia. Population research in a sample of 1259 men in Finland found that those in the highest quartile of daily phosphatidylcholine intake have a 28% lower risk of being diagnosed with dementia than those in the lowest quartile, over a mean follow-up of about 22 years (103178).
• Fatty deposits. Preliminary clinical evidence suggests that subcutaneous injections of phosphatidylcholine can reduce localized fatty deposits on the chin, thigh, hips, abdomen, back, neck, and elsewhere, based on subjective visual assessments (15621,15625,15627). Improvements appear to last for 2-3 years or longer (15621,15627). In one study, phosphatidylcholine injections markedly or moderately reduce localized fatty deposits on the face in about 80% of patients for a period of up to 3 years based on subjective patient self-assessment (15621). The findings of these studies are severely limited by poor study quality.
• Hepatic encephalopathy. Clinical research suggests that taking polyunsaturated phosphatidylcholine 1050 mg daily for 6-8 weeks, either orally or through a nasogastric tube, does not improve recovery from encephalopathy compared with control in patients with acute or subacute liver failure. However, polyunsaturated phosphatidylcholine seems to reduce mortality compared to control in patients with subacute, but not acute, liver failure (68835).
• Hepatitis B. Clinical research using phosphatidylcholine for hepatitis B show conflicting results (5224,5226).
• Hepatitis C. Preliminary clinical research suggests that taking the polyunsaturated form of phosphatidylcholine orally, in combination with interferon, seems to help reduce liver enzymes in patients with chronic hepatitis C (5226).
• Hyperlipoproteinemia. Clinical research suggests that taking polyunsaturated phosphatidylcholine 1.8 grams daily for 28 days in combination with clofibrate does not significantly reduce total cholesterol, triglycerides, or phospholipids compared to clofibrate alone in patients with primary hyperlipoproteinemia of Fredrickson Types II or IV. However, taking the combination of polyunsaturated phosphatidylcholine plus clofibrate seems to significantly attenuate the relative increase in low-density lipoprotein (LDL) cholesterol compared to clofibrate alone (68840).
• Lipoma. An anecdotal report suggests that injecting a phosphatidylcholine solution directly into a lipoma can shrink the tumor by about 35%. However, in this report a major inflammatory reaction occurred, resulting in undesirable fibrotic changes to the tissue and eventual surgical excision of the lipoma (15622).
• Memory. Preliminary clinical evidence shows that taking a single dose of phosphatidylcholine 25 grams (PC-55, TwinLab) can improve some measures of memory in healthy college students (5228).
• Nonalcoholic fatty liver disease (NAFLD). Preliminary clinical research shows that taking phosphatidylcholine 600 mg orally three times daily for 24 weeks qualitatively improves liver echogenicity and structure on an ultrasound scan, suggesting a reduction in hepatic steatosis. There is also a small decrease in liver function test values, but with considerable variability both at baseline and at 24 weeks (103176,103177). Preliminary clinical evidence also suggests that taking a combination of the milk thistle constituent silybin, phosphatidylcholine, and vitamin E (Realsil, Instituto Biochimico Italiano) orally twice daily for 12 months improves liver function tests (LFTs) and liver histology in people with NAFLD (63244).
• Periorbital fat pad herniation. Preliminary clinical research suggests that injecting a phosphatidylcholine solution markedly reduces lower eyelid fat pads in people with bulging fat pads due to herniation. In some people, benefits appeared to last for a period of 9 months to 2 years or longer (15623,15628). More evidence is needed to rate phosphatidylcholine for these uses.

(Read more about PHOSPHATIDYLCHOLINE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. It is unclear if dietary citrus fruits are beneficial in patients with asthma. Details: There is some evidence that consumption of vitamin C-rich citrus fruits, including sweet orange and others, might improve lung function in people with asthma. However, this is controversial. Some studies show that intake of citrus fruits 1-2 times per week produces significant benefit (6049,6055,6056), while other studies have not found this benefit (6057,6058).
• Common cold. It is unclear if drinking sweet orange juice prevents the common cold. Details: Preliminary clinical research in healthy individuals ages 17 to 25 years suggests that drinking sweet orange juice 180 mL daily for 72 days might decrease the risk of developing common cold-related symptoms (15328).
• Depression. It is unclear if drinking sweet orange juice or using sweet orange essential oil as aromatherapy is beneficial for depression. Details: Preliminary clinical research in adults with depression shows that drinking flavonoid-rich sweet orange juice 190 mL three times daily for 8 weeks modestly improves depression scores when compared to baseline, but not when compared with a low-flavonoid orange drink (110045). Sweet orange has also been studied as part of a combination aromatherapy. A very small clinical study in community-dwelling older adults shows that massage therapy to the upper body with sweet orange, lavender, and bergamot oils twice weekly for 8 weeks improves symptoms of depression in 65% of patients when compared with no intervention. Twice weekly inhalation of the same essential oils via nebulizer, without massage, also improves symptoms of depression in 55% of patients when compared with no intervention (98474).
• Hypercholesterolemia. It is unclear if drinking sweet orange juice improves blood lipid levels. Details: A very small clinical study in hypercholesterolemic patients shows that drinking large amounts of sweet orange juice (750 mL daily for four weeks) seems to increase high-density lipoprotein (HDL) cholesterol by 21% and reduce the ratio of low-density lipoprotein (LDL) to HDL cholesterol by 16% when compared to baseline. This effect was not seen with 250-500 mL of sweet orange juice. Because consumption of this large amount of juice daily provides approximately 20% of the daily energy requirement, this regimen may not be practical (3340).
• Insomnia. Sweet orange essential oil as aromatherapy has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: Preliminary clinical research in adults undergoing hemodialysis shows that inhaling aromatherapy with sweet orange and lavender oil nightly before bed for one month improves overall sleep quality by 72% and fatigue by about 78% when compared with no treatment (98508).
• Kidney failure. It is unclear if sweet orange oil massage can improve fatigue or symptoms of restless leg syndrome (RLS) in adults receiving hemodialysis. Details: A small clinical study shows that receiving an 18-minute foot massage with sweet orange oil 1.5% for 3 weeks during hemodialysis sessions modestly improves sleep quality and symptoms of RLS when compared with routine care. However, it does not seem to be more effective than using lavender oil (109859).
• Kidney stones (nephrolithiasis). It is unclear if drinking sweet orange juice is beneficial for preventing kidney stones. Details: Consuming 400 mL of sweet orange juice three times a day, providing a total of 100 mEq of citrate daily, increases urinary pH and urinary citrate levels (15171). Theoretically, this might reduce kidney stone formation in patients with calcium nephrolithiasis. However, this outcome has not been evaluated in clinical research.
• Obesity. It is unclear if drinking sweet orange juice or taking oral sweet orange extract improves weight loss or other metabolic parameters in adults with overweight or obesity. Most studies suggest that any effects are unlikely to be considered clinically relevant. Details: Some preliminary clinical research in adults with overweight or obesity shows that taking a specific sweet orange extract (Morosil, Bionap S.R.L.) 400 mg orally once daily for six months reduces waist circumference, body weight, fat mass, and body mass index (BMI) by 2% to 5% when compared with placebo (110046). However, other preliminary clinical research in this population shows that drinking red sweet orange juice 750 mL daily for 8 weeks does not reduce body weight or BMI when compared with baseline (92309). A meta-analysis of clinical research in adults, most of whom were overweight or obese at baseline, shows that drinking 250-750 mL of various types of sweet orange juice daily for 2-12 weeks does not reduce body weight, BMI, waist circumference, or body fat percentage (BFP) when compared with control groups, which included either no supplementation, pomegranate juice, or exercise (107853). The validity of this meta-analysis is limited due to the population heterogeneity and variety of orange juice formulations and controls utilized. Some clinical studies have also evaluated sweet orange juice for improving cardiovascular risk factors in overweight and obese adults. Although some research has shown benefit, not all research agrees (110046,110047). A meta-analysis of randomized clinical trials in adults with overweight or obesity shows that drinking sweet orange juice 250-600 mL daily for 2-13 weeks modestly increases high-density lipoprotein cholesterol levels and decrease average systolic blood pressure by 1 mmHg when compared with control. However, drinking sweet orange juice does not affect other blood lipid levels, blood glucose levels, or markers of insulin resistance (110048). The validity of this study is limited by high heterogeneity and a small sample size. In addition, these improvements are unlikely to be considered clinically relevant. Sweet orange extract has also been studied in combination with other ingredients. Some clinical research in overweight adults shows that taking a specific combination product (Sinetrol, Fytexia) 450-700 mg twice daily containing sweet orange, blood orange, and grapefruit extracts for 12 weeks reduces body weight, BFP, and BMI when compared with placebo or baseline (95517,95518). It is unclear if these effects are due to sweet orange, other ingredients, or the combination.
• Pre-procedural anxiety. It is unclear if inhaling sweet orange essential oil as aromatherapy reduces anxiety before surgeries or invasive procedures. Details: A small, low-quality study suggests that inhaling the scent from 3 drops of sweet orange essential oil applied to a cotton ball for 5 minutes modesty reduces anxiety and pain scores in patients undergoing needle insertion for hemodialysis when compared with performing a breathing exercise for 3 minutes (105455).
• Prostate cancer. It is unclear if drinking sweet orange juice reduces prostate cancer risk. Details: Observational research has found that increasing dietary intake of sweet orange or sweet orange juice is not associated with a reduced risk of developing prostate cancer (15172).
• Stress. It is unclear if inhaling sweet orange essential oil as aromatherapy is beneficial for stress. Details: Preliminary clinical research shows that using up to 10 drops of sweet orange essential oil as aromatherapy helps prevent some anxiety and tension associated with stressful tasks when compared with control (90505). More evidence is needed to rate sweet orange for these uses.

(Read more about SWEET ORANGE)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Dandelion has Generally Recognized As Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those in foods.

(Read more about DANDELION)

LIKELY SAFE ...when the root preparations are used in amounts commonly found in foods. Gentian root is categorized by the FDA as a safe food additive flavoring in the US (4912).

POSSIBLY SAFE ...when gentian root is used orally in a specific combination that contains gentian root, elderflower, verbena, cowslip flower, and sorrel (SinuComp, Sinupret) (374,379,95907). There is insufficient reliable information available about the safety of the topical use of gentian.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of gentian in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about GENTIAN)

LIKELY SAFE ...when consumed in amounts commonly found in food. Myrrh is approved for use in foods as a flavoring agent in the US (11).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Myrrh 400 mg three times daily has been safely used for up to 12 months (93653,104593). Myrrh 500 mg three times daily has been used with apparent safety for 2 weeks (104840). ...when used topically and appropriately (2,4,5,11,18). As a diluted bath, myrrh has been used with apparent safety for up to 7 days (104838,104839).

POSSIBLY UNSAFE ...when used orally in excessive doses. Myrrh may cause kidney irritation and diarrhea when used in doses of 2-4 grams (12).

PREGNANCY: LIKELY UNSAFE
when used orally. Myrrh stimulates uterine tone and blood flow and may have an abortifacient effect (4,12,19,93645). There is insufficient reliable information available about the safety of the topical use of myrrh during pregnancy.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about MYRRH)

POSSIBLY SAFE ...when used orally and appropriately. Large doses up to 30 grams per day for 6 weeks (5223) and smaller doses of up to 6 grams daily for up to 24 months have been well tolerated (68839,68843,105728). ...when used subcutaneously and appropriately, short-term. Some research suggests that subcutaneous injections of 0.2 mL to 5 mL of a 5% phosphatidylcholine solution do not cause significant serious adverse effects when doses are administered up to five times and spaced apart by 2-4 weeks (15621,15623,15624,15625). ...when used topically as an emulsion also containing niacinamide for up to 12 weeks (93388).

PREGNANCY: POSSIBLY SAFE
when used orally from 18 weeks of gestation at doses of up to 5 grams daily (93386)

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PHOSPHATIDYLCHOLINE)

LIKELY SAFE ...when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340,15171,92309).

POSSIBLY SAFE ...when the essential oil of sweet orange is inhaled as aromatherapy, short-term (35735,58060,90505,105455). There is insufficient reliable information available about the safety of sweet orange peel when used orally.

CHILDREN: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods.

CHILDREN: POSSIBLY UNSAFE
when the sweet orange peel is used orally in excessive amounts. There have been reports of intestinal colic, convulsions, and death in children given large amounts of sweet orange peel (11).

PREGNANCY AND LACTATION: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.  Details In vitro research suggests that dandelion root inhibits platelet aggregation (18291).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.  Details Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion (13474,90926). Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion (46960).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.  Details Laboratory research suggests that dandelion might inhibit CYP1A2 (12734). So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.  Details There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme (12734).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.  Details Animal research suggests that dandelion has diuretic properties (13475). As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.  Details Dandelion contains significant amounts of potassium (13465).

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might lower fluoroquinolone levels.  Details Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73% (13477). However, this effect has not been reported in humans.

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, myrrh might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details In vitro and animal research suggests that myrrh has hypoglycemic effects (4,104841).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, myrrh might decrease the effectiveness of warfarin.  Details In one case, a patient who was previously stable on warfarin had a significant decline in international normalized ratio (INR) following consumption of an aqueous extract of myrrh (14425).

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CELIPROLOL (Celicard) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange with celiprolol can decrease oral absorption of celiprolol.  Details A pharmacokinetic study in healthy volunteers shows that celiprolol levels, after a single dose of 100 mg, are decreased by up to 90% in people who drink sweet orange juice 200 mL three times daily. It's not known if lower consumption of sweet orange juice will have the same effect. Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (12115,17603,17604). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).

FEXOFENADINE (Allegra) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice with fexofenadine can decrease oral absorption of fexofenadine.  Details Clinical research shows that coadministration of sweet orange juice 1200 mL decreases bioavailability of fexofenadine by about 72% (7046,17604). In an animal model, sweet orange juice decreased bioavailability of fexofenadine by 31% (17605). Fexofenadine manufacturer data indicates that concomitant administration of sweet orange juice and fexofenadine results in larger wheal and flare sizes in research models. This suggests that sweet orange reduces the clinical response to fexofenadine (17603). Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (7046). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).

IVERMECTIN (Stromectol, others) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice with ivermectin can decrease the oral absorption of ivermectin.  Details A pharmacokinetic study in healthy volunteers shows that taking ivermectin orally with sweet orange juice 750 mL over 4 hours reduces the bioavailability of ivermectin. This effect does not seem to be related to effects on P-glycoprotein. The effect on ivermectin is more pronounced in males compared to females (12154).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice can decrease oral absorption of OATP substrates. Separate administration by at least 4 hours.  Details Clinical research shows that consuming sweet orange juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP (17603,17604). For example, sweet orange juice decreases bioavailability of fexofenadine, a substrate of OATP, by about 72% and of celiprolol, another OATP substrate, by up to 90% (7046,12115). Since sweet orange juice seems to affect OATP for a short time, recommend separating drug administration and consumption of sweet orange juice by at least 4 hours (17603,17604).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.  Details Animal and in vitro research suggest that orange juice extract inhibits drug efflux by P-gp, increasing absorption and levels of P-gp substrates (12116,15327). In contrast, pharmacokinetic research in humans shows that drinking large amounts of sweet orange juice decreases absorption and levels of the P-gp substrate celiprolol. This suggests that orange juice actually induces drug efflux by P-gp or affects drug levels by another mechanism such as inhibiting the gut drug transporter called organic anion transporting polypeptide (OATP) (7046,12115). Until more is known, sweet orange juice should be used cautiously in people taking P-gp substrates.

PRAVASTATIN (Pravachol) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice with pravastatin can increase the absorption of pravastatin.  Details A small pharmacokinetic study in healthy volunteers shows that consuming sweet orange juice 800 mL over 3 hours, including before, during, and after taking pravastatin 10 mg, increases pravastatin levels by about 149%, without affecting pravastatin elimination. Theoretically this effect might be due to modulation of organic anion transporting polypeptides (OATPs) by sweet orange juice (14348). Sweet orange juice does not seem to affect simvastatin levels, but it is not known if sweet orange affects any of the other statins.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Calcium-fortified sweet orange juice might reduce quinolone absorption.  Details Calcium binds to quinolones in the gut. Theoretically, the calcium in certain fortified orange juices can also bind to quinolone antibiotics and reduce their absorption and levels (4412,10339,13714,21638,38570).

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General ...Orally, dandelion seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, heartburn, and stomach discomfort.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Cardiovascular ...In one report, a 39-year-old obese woman developed palpitations and syncope after taking a weight loss supplement containing a combination of dandelion, bladderwrack, and boldo for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether dandelion, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.

Dermatologic ...Topically, dandelion can cause contact dermatitis and erythema multiforme in sensitive individuals. Dandelion can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (13478,13481,42893,46945,46977). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Endocrine ...In one report, a 56-year-old man with renal impairment developed hyperoxalaemia and peripheral gangrene after ingesting large amounts of dandelion tea (10 to 15 cups daily for 6 months). The adverse effect was attributed to the high oxalate content of dandelion tea (258 mcmol/L) and reduced renal oxalate clearance caused by renal impairment (90639). In another report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemic symptoms 2 weeks after beginning to eat salads containing dandelion (46960). The hypoglycemic effect was attributed to the potential alpha-glucosidase inhibitory activity of dandelion.

Gastrointestinal ...Gastrointestinal symptoms, including stomach discomfort, diarrhea, and heartburn, have been reported following oral use of dandelion (19146,36931). A case of intestinal blockage has been reported for a patient who ingested a large amount of dandelion greens three weeks after undergoing a stomach operation (46981). Also, a case of hemorrhagic cystitis has been reported for a 33-year-old woman who took a specific herbal product (Slim-Kombu, Balestra and Mech, Vicenza, Italy) containing 20 herbal extracts, including dandelion extract. Symptoms resolved after the patient discontinued using the product, and symptoms resumed when the patient began taking the supplement again four months later. While various ingredients in the supplement may have contributed to the symptoms, it is possible that dandelion extract may have contributed to the effect due to its diurectic, laxative, cholagogue, and antirheumatic properties (46959).

Other ...Orally, products containing dandelion pollen can cause allergic reactions, including anaphylaxis (13479,13480). Also, rhinoconjunctivitis and asthma have been reported after handling products such as bird feed containing dandelion and other herbs, with reported positive skin tests for dandelion hypersensitivity (46948). Dandelion pollen may cause pollinosis, such as allergic rhinitis and conjunctivitis (18065,46951,46964,46966,46972).

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General ...Orally, gentian root, in combination with other herbs, seems to be generally well tolerated (95907). Side effects reported in clinical studies include gastrointestinal discomfort and allergic skin reactions (374,379). There is insufficient reliable information available about the adverse effects of gentian when taken as a medicine alone.

Gastrointestinal ...Orally, gentian root, in combination with other herbs, has been reported to cause gastrointestinal adverse effects (374,379). Gastrointestinal intolerance occurred in patients with cancer-associated anorexia who took gentian tincture 1 mL three times daily, in conjunction with turmeric 1 gram and ginger 1 gram twice daily, for 14 days. Six of 17 patients discontinued the regimen due to nausea, 3 due to vomiting, 2 due to diarrhea, and 2 due to bloating. It is unclear if this gastrointestinal intolerance was caused by gentian, the other herbs, or the patients' predisposing conditions (96263).

Immunologic ...Orally, gentian root, in combination with other herbs, has been reported to cause allergic skin reactions (374,379). It is unclear if these reactions were caused by gentian, the other herbs, or the combination.

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General ...Orally, myrrh seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Kidney impairment and heart rate changes at high doses.

Cardiovascular ...Orally, myrrh taken at doses of 2-4 grams may cause heart rate changes in some patients (12,19).

Dermatologic ...Topically, myrrh has been reported to cause dermatitis (6).

Gastrointestinal ...Orally, myrrh may cause diarrhea in some patients when taken at doses of 2-4 grams (12,19).

Genitourinary ...Severe lower abdominal pain has been reported in a pregnant woman drinking myrrh resin dissolved in 500 mL of water twice daily as prescribed by a traditional practitioner. This adverse effect resolved one day after discontinuing myrrh. The investigators suggest that this acute abdominal pain was related to myrrh's activity as a uterine stimulant (93645).

Immunologic ...Orally, myrrh has been reported to cause severe allergic skin reactions, with redness, swelling, and itching, in two case reports of individuals using oral traditional Chinese medicines containing myrrh (101114).

Renal ...Orally, myrrh may cause kidney impairment in some patients when taken at doses of 2-4 grams (12,19).

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General ...Phosphatidylcholine is generally well tolerated when used orally, subcutaneously, or topically. Orally, bloating, diarrhea, altered taste, nausea, vomiting, sweating, and itching have been reported with phosphatidylcholine (5229,63244,68843,93389,93390,105728). Ingesting large amounts of around 30 grams daily is associated with a higher incidence of gastrointestinal upset and diarrhea (5223). Subcutaneously, pain, burning, itching, tenderness to touch, bruising, edema, nodules, hematoma, and erythema at the injection site have been reported with phosphatidylcholine (1562,15623,15624,15625,15626,15627,15628). High subcutaneous doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624). Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissues changes (15622).

Dermatologic ...When taken orally, phosphatidylcholine may increase sweating (5229) and itching (63244). When given subcutaneously, phosphatidylcholine can cause pain, burning, itching, tenderness to touch, bruising, edema, and erythema at the injection site. The pain, itching and erythema usually resolve within 2 days of treatment; however localized tenderness can last longer (15623,15624,15626,15627,15628). Edema and bruising usually resolve within 10 days of treatment (15621,15623,15625). Some people can also develop nodules or hematoma at the injection site. This usually resolves within 30 days (15627).

Gastrointestinal ...Ingesting large amounts of phosphatidylcholine (30 grams per day) can cause gastrointestinal upset and diarrhea (5223). However, bloating, diarrhea, altered taste, nausea, and vomiting have been reported with smaller doses (63244,68843,93389,93390,105728). Although moderate subcutaneous doses do not usually cause systemic side effects, high doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624).

Musculoskeletal ...Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissue changes (15622).

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General ...Orally, sweet orange juice or fruit seem to be well tolerated. Large amounts of sweet orange peel may be unsafe, especially for children. When inhaled, sweet orange essential oil seems to be generally well tolerated.

Gastrointestinal ...There have been reports of intestinal colic in children following ingestion of large amounts of sweet orange peel (11).

Neurologic/CNS ...There have been reports of convulsions in children following ingestion of large amounts of sweet orange peel (11).

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